Thymic hyperplasia is accurate to detect new-onset Graves' hyperthyroidism and resolves after restoring euthyroidism.

PURPOSE: Abnormal liver blood tests (ALBTs), neutropenia (NEU) and thymic hyperplasia (TH) are new features of Graves' disease (GD). Our objectives were: (a) to calculate the accuracy of TH in discriminating between Graves' and non-Graves' thyrotoxicosis, compared to ALBTs, NEU and Graves' orbitopathy (GO); (b) to explore the outcome of GD-associated TH and non-GD-associated TH. METHODS: We prospectively analyzed consecutive adult patients with newly diagnosed thyrotoxicosis from January 2018 to June 2023. TH was detected via neck ultrasound (nUS) then confirmed and followed by magnetic resonance imaging (MRI). For GD vs non-GD clinical sensitivity (SE) and specificity (SPEC), accuracy, positive predictive value (PPV) and negative predictive value (NPV) of GO, TH, ALBTs and NEU were calculated. RESULTS: 264 thyrotoxic patients were included. TH was found in 16.4% (20/122) of GD vs 1.4% (2/142) in non-GD (p < 0.001). SE, SPEC, accuracy, PPV and NPV of the four extrathyroidal manifestations of GD were as follows, respectively: GO 26%, 100%, 66%, 100%, 61%; ALBTs 41%, 89%, 69%, 76%, 66%; NEU 5%, 100%, 56%, 100%, 55%; TH 16%, 98%, 61%, 91%, 98%. In 18 of them, TH regressed within 12 months after achieving euthyroidism under anti-thyroid drug therapy, while in the remaining 2, TH regressed 6 months after thyroid surgery. In the two non-GD patients with TH, thymus disappeared along with euthyroidism. CONCLUSIONS: TH in the hyperthyroidism scenario provides a high PPV for GD. A conservative approach for the diagnostic work-up and initial management of thyrotoxicosis-associated TH should be adopted.

Perspectives of nuclear diagnostic imaging in diabetic cardiomyopathy.

Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance. Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function. In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents. A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy.

Evaluation of cardiac and respiratory involvement in sarcoglycanopathies.

Sarcoglycanopathies constitute a subgroup of limb-girdle recessive muscular dystrophies due to defects in sarcoglycan complex that comprises five distinct transmembrane proteins called alpha-, beta-, gamma-, delta-and epsilon-sarcoglycans. As it is well known that sarcoglycans are expressed both in heart and in skeletal muscles and a complete deficiency in delta-sarcoglycan is the cause of the Syrian hamster BIO.14 cardiomyopathy, we studied cardiac and respiratory involvement in 20 patients with sarcoglycanopathies by clinical, electrocardiographic, echocardiographic, scintigraphic and spirometric assessments. A normal heart function was found in 31.3% of all patients; a preclinical cardiomyopathy in 43.7%; an arrhythmogenic cardiomyopathy in 6.3% and initial signs of dilated cardiomyopathy in 18.7%. In one patient the data were examined retrospectively. No correlation was found between cardiac and skeletal muscle involvement. With reference to the type of sarcoglycanopathy, signs of hypoxic myocardial damage occurred in beta-, gamma- and delta-sarcoglycanopathies, while initial signs of a dilated cardiomyopathy in gamma- and delta-sarcoglycanopathies were found. A normal respiratory function was observed in 23.5% of all patients, a mild impairment in 35.4%, a moderate impairment in 29.4%, and a severe impairment in 11.7%.

Left ventricular function and perfusion in Becker's muscular dystrophy.

UNLABELLED: The aim of this study was to evaluate left ventricular (LV) perfusion and function in patients with Becker muscular dystrophy (BMD). METHODS: Fourteen male patients (age range 14-40 yr) with BMD were evaluated by 201Tl SPECT and radionuclide angiography both at rest and after dipyridamole stress test. RESULTS: All patients showed uptake defect demonstrated by 201Tl SPECT (mean 4.1 +/- 2.2 uptake defect/patient). Significant relationships (p < 0.05) were found between the number of uptake defects and rest LV ejection fraction (LVEF) (r = -0.54); peak filling rate (PFR) (r = -0.57) and dipyridamole LVEF (r = -0.65). Dipyridamole induced reversible uptake defects were found in 7/14 (50%) patients with BMD. The 14 patients were divided into two groups on the basis of the presence (Group A, n = 6) or the absence (Group B, n = 8) of severe irreversible uptake defect (i.e., < 50% 201Tl uptake). Group A showed lower values of PFR and LVEF when compared to patients of Group B. CONCLUSIONS: In patients with BMD there is a relatively high incidence of uptake defects and LV function (both at rest and after dipyridamole) appears to be related to the number of uptake defects. Moreover, the presence of severe irreversible uptake defects identifies a subgroup of patients with BMD characterized by a severely depressed LV function.

Diagnosis and radioguided surgery with 111In-pentetreotide in a patient with paraneoplastic Cushing's syndrome due to a bronchial carcinoid.

In a 28-year-old man with Cushing's syndrome, studies investigating a hypophyseal and/or adrenal origin of the disease, including computed tomography and magnetic resonance imaging, were negative. In agreement with reports showing somatostatin receptors on the cell membrane of ectopically secreting ACTH tumours, scintigraphy was performed after intravenous injection of 111 MBq 111In-pentetreotide (OCT). The radiolabelled OCT scan showed a small focal area of intense uptake at the inferior lobe of the right lung. Subsequent radioguided surgery located and defined a small mass (1.8 x 1.4 x 1.6 cm). The probe pinpointed the mass to the right inferior chest lobe, with a tumour/normal tissue count ratio of 6:1 and tumour/hilar normal lymph node ratio of 12:1, thus permitting the complete excision of the tumour to exclude lymph node and/or parietal involvement. A lung carcinoid was diagnosed at histology. The patient is still alive and disease-free 24 months after surgery. 111In-OCT was found to be useful for localizing the ACTH-secreting tumour and also permitted rapid non-invasive differential diagnosis between an ACTH-secreting pituitary adenoma and malignancy causing ectopic ACTH syndrome. This study also showed the clinical usefulness of radioguided surgery in the treatment of bronchial carcinoid.

Receptor imaging with 111In-pentreotide and 123I-methoxybenzamide, and inhibition tests with octreotide and bromocriptine of mixed growth hormone/prolactin-secreting pituitary tumors.

We have performed pituitary scintigraphy with 111In-pentreotide (OCT), a somatostatin analogue, and with metoxybenzamide (IBZM) by 123I-IBZM in two patients affected by mixed growth hormone/prolactin-secreting pituitary tumors. Short-term growth hormone (GH) inhibition by a single injection of OCT (100 micrograms s.c.), and short-term prolactin (PRL) inhibition by oral administration of 2.5 mg of bromocriptine (BCR), were also performed in both patients. The first patient, a 26 year old man, showed intense tumor uptake of 123I-IBZM scintigraphy, whereas 111In-OCT scintigraphy showed moderate tumor uptake. Five hours after the BCR inhibition test, a fall of 83% in PRL plasma levels (from 8,336 micrograms/L to 1,417 micrograms/L), and of 91.6% in GH plasma levels (from 39.5 micrograms/L to 3.3 micrograms/L) were observed. OCT inhibition test suppressed GH plasma levels from 36 micrograms/L to 3.5 micrograms/L. The patient was submitted to treatment with BCR and OCT. A dramatic shrinkage of the tumor was seen after six months of therapy. The lesion disappeared one year after the start of therapy. The second patient, a 64 year old man, showed intense uptake at 111In-OCT scintigraphy, while 123I-IBZM uptake was not observed. A test dose of BCR resulted in an acute fall of PRL (from 145 micrograms/L to 118 micrograms/L), but not of GH. A test dose of OCT decreased the GH plasma level from 61 micrograms/L to 4.5 micrograms/L. The patient was submitted to treatment with BCR and OCT that resulted in a computed tomography and magnetic resonance imaging decrease of 45% of tumor volume one year after the start of therapy. Our results suggest that both suppression tests with OCT and BCR, and scintigraphic studies in vivo with 123I-IBZM and 111In-OCT can be predictive for the effectiveness of therapies with dopamine agonists and/or SS-analogs in patients with mixed PRL/GH-secreting pituitary tumors. Further studies are required to evaluate the role of suppressive tests in selecting patients for appropriate clinical treatments.

[Immunological imaging using tagged octreotide]. / Imaging immunologico con octreotide marcato.

The diagnostic use of radiolabeled octreotide has shown that somatostatin receptor scintigraphy can be successfully used in various neoplasms with a strictly neuroendocrine derivation, because of a good correlation between in vitro receptor expression and in vivo uptake. Moreover, 111In-Octreotide uptake has been demonstrated in various pathologies owing to the receptorial expression on cell elements such as lymphocytes, fibroblasts and endothelium. Although main diagnostic role is in neuroendocrine tumours, octreotide can be also used to obtain an immunological imaging in other fields. The presence of type 2 receptors on activated lymphocytes has stimulated the use of somatostatin in both the treatment and diagnosis of disease activity in patients with Graves' ophthalmopathy. Somatostatin analogs have been successfully used for the treatment and imaging of various tumours of thymic origin. Our research group has evaluated the possible clinical role of octreotide scintigraphy in paediatric patients with thymic hyperplasia after chemotherapy for lymphoma. Even if not routinely applicable, these approaches offer interesting diagnostic, prognostic and therapeutic prospects.

[Role of somatostatin analogs in the treatment of neuroendocrine tumours]. / Ruolo degli analoghi della somatostatina nella teapia dei tumori neuroendocrini.

Current therapeutic approaches in neuroendocrine tumours include surgery, radiotherapy and polychemotherapy. Different metabolic patterns of neuroendocrine tumours allow the use of a wide range of diagnostic options in nuclear medicine, due to the presence of a wide spectrum of radiotracers electively concentrating in these neoplasms. Nuclear medicine, and in particular 111In Octreotide (OCT) scintigraphy, 123I Methaiodobenzylguanidine (MIBG) and pentavalent 99mTc-DMSA (V-DMSA), together with biohumoral markers, are currently able to locate tumours also not detectable using traditional diagnostic techniques. Somatostatin analogs, such as octreotide have become increasingly important over the years in the treatment of patients with neuroendocrine tumours. At present the therapeutic use of somatostatin analogs can be schematised as 1) pharmacological treatment (with cold octreotide); 2) surgical treatment (radioguided surgery); 3) radiometabolic treatment (with marked octreotide). The development of new synthetic molecules and new radiocompounds will probably open up interesting scenarios in the near future.

[Role of radio-guided surgery with 111In-octreotide in the treatment of thoracic neoplasms]. / Ruolo della chirurgia radio-guidata con in-octreotide nel trattamento delle neoplasie toraciche.

The study evaluates the role of radio-guided surgery (RGS) with 111In-octreotide in the treatment of lung neoplasms. RGS with octreotide appears to be useful in surgery, above all during the intraoperative staging of the tumour; it can define with greater precision the extent of the resections extended towards the lung wall and ensure a radical approach in minimal lung resections.

Immunoscintigraphy as an adjunct to diagnostic imaging in septic sacroiliitis. Report of a case.

Septic sacroiliitis in childhood is a relatively rare condition. We describe a case of septic sacroiliitis occurring in an 11-year-old girl in whom the diagnosis was suspected on clinical findings and bone scan. Immunoscintigraphy with 99mTc-labelled antigranulocyte antibodies further supported the hypothesis for a septic origin of the disease. The clinical evolution clinched the diagnosis.

Breast cancer detection with Tc-99m tetrofosmin.

Myocardial SPECT imaging was performed with Tc-99m tetrofosmin. Intense focal uptake at the level of the left breast was observed. At mammography a breast carcinoma was suspected, which was confirmed after surgery. This may be the first report of neoplastic mammary uptake of Tc-99m tetrofosmin.

Kinetics of Tc-99m sestamibi and Tc-99m tetrofosmin in a case of parathyroid adenoma.

The uptake of Tc-99m tetrofosmin (TF) is reported in a case of parathyroid adenoma. A 65-year-old woman was studied on different days with TF, Tc-99m sestamibi (MIBI) and Tl-201 chloride (Tl). TF and MIBI injections were preceded by oral administration of potassium perchlorate. Clear identification of the adenoma was observed in all scans. No further information was obtained using a subtraction technique with Tc-99m pertechnetate. Regarding the thyroid/parathyroid ratio, different kinetics between TF and MIBI appear to be demonstrated. In particular, thyroid washout was observed with MIBI but not with TF.

[Preliminary experience with radioimmuno-guided surgery of primary neoplasms of the lung]. / Esperienze preliminari sulla chirurgia radioimmunoguidata delle neoplasie primitive del polmone.

BACKGROUND: Radioimmunoguided surgery (RIGS) can be a valid option in the management of lung cancer as well as neoplasms in other anatomic sites. METHODS: We evaluated the usefulness of radioimmunoguided surgery (RIGS) in the staging of primitive non small cell lung cancer. Intraoperatively, this technique can define the lymph nodes involvement and thus, the radicality of the resection. In the first stage of our study, we looked for the epitope TAG 72 in 45 patients with primary non small cell lung cancer. The epitope was found by immunochemistry in only 6 cases. The only one operable patient was injected with monoclonal antibody B 72.3, that was 125I-labelled. RESULTS: At the operation, the monoclonal antibody showed no selectivity for neoplastic cells. Neoplastic tissue and healthy tissue showed a similar detection of the monoclonal antibody both intraoperatively and at the histochemical study. Because of the problems related with this method--e.g. technical difficulties, excessive wasting of time and lack of imaging--we modified our strategy. In this second stage of our study we used fragments of murine anti-CEA monoclonal antibody F023C5. The protocol was performed in 11 patients with squamous cell lung cancer. In one patient operated on for an excavated cancer(not well-defined at the immunoscintigraphy) intraoperative detection was negative while the ex vivo counts were significant: the neoplastic tissue showed a radioactivity twice higher than healthy tissue. Furthermore, the RIGS found a small intraparenchimal lymph node that was seen neither by CT nor by immunoscintigraphy. CONCLUSIONS: Our data are still preliminary, but with improvement of the technique and the use of more specific monoclonal antibodies the RIGS could become a helpful method, able to improve the radicality of surgery for lung cancer.

[Modulation of the axillary lymph node dissection in breast cancer]. / La modulazione della dissezione linfonodale dell'ascella nel carcinoma mammario. Nostra esperienza.

UNLABELLED: Several studies showed the reliability of the sentinel lymph node (SN) technique in the evaluation of the N parameter in breast cancer so much to induce surgeons to limit the axillary dissection to the biopsy of the SN alone (SNB) in case this is negative to the extemporaneous examination. After a period of focusing on the identification technique, biopsy and histological examination of the SN (October 97-January 98) always followed by a complete dissection of the three axillary node levels (ALND), we started a study to evaluate the reliability of a limited dissection of the 1st level of the axilla (FLND) in women with T < 3 cm, N0-1a, M0, that did not undergo any neoadjuvant treatment and in which the SN resulted free from metastases. We started this phase of the study in February 1998 till May 2001. In the present paper we show the results related to this period. MATERIALS AND METHODS: We enrolled 256 women with T < 3 cm, N0-1a, M0. In 49 cases we used vital dye, in 23 dye + radioguided surgery (RGS) and in 184 RGS only. The extemporaneous histological examination of the SN has been performed with thin sections, dyed with EE. When SN was negative to the intraoperative examination, we limited the dissection to the 1st level of the axilla, except that in 3 patients, with SN located to the 2nd level, in which we did an ALND. The FLND has been performed in 17 cases with a minimally invasive technique. The definitive histological examination of the SN always included the immunohistochemistry. If the SN was positive, usually underestimated to the intraoperative examination, the patients had an adjuvant chemotherapy. RESULTS: In 203/207 patients (98.1%) SN was found to the pre-operative lymphoscintigraphy. During surgery the SN was identified in 46/49 (94%) using the vital dye, in 22/23 (96%) using the vital dye + RGS and in 176/179 (98.3%) using RGS. To the extemporaneous histological examination SN was negative in 140, metastatic in 101; to the histological definitive results of the SN we noticed 6 false negative, since others lymph nodes than SN were positive (4 cases) or for evidence of micrometastases at the immunohistochemistry which were not detected at the extemporaneous examination (2 cases). On 107 cases of N+ the SN was the only metastatic lymph node in 42 (39.3%). The false negative percentage was 5.6% and the diagnostic accuracy of the SNB was 97.5%. In the group treated with FLND we only noticed two cases of light lymphedema (1.4%). CONCLUSIONS: Our results are in concordance with the international literature and they induced us, from June 2001, to begin a new phase of the study in which we limit the dissection of the axilla to the SN only, if not metastatic, in women with T1 breast carcinoma.

The present and future role of (111)In pentetreotide in the PET era.

Today, positron emission tomography (PET) using F-18 Fluoro-deoxyglucose (FDG) is, when available, the most important nuclear medicine procedure applied to oncology. Nevertheless, 2 main reasons for the clinical use of somatostatin analogues labeled with single photon emitting radionuclides are: a) the low accuracy of PET-FDG in neuroendocrine tumors (NET); b) the expression of somatostatin receptors (sstr) in most cells deriving from so-called neuroendocrine dispersed cells. The latter forms the premise for the use of radiolabeled somatostatin analogues, and (111)In pentetreotide (Octreo-scan) in particular, in the diagnosis of NET and other pathological conditions, including some benign diseases. Alongside diagnosis, staging and follow-up of NET, somatostatin analogues, whether radiolabeled or not, can have a role in evaluating prognosis and predicting therapeutic efficacy in cancer patients. Interesting indications have emerged with radioguided surgery and in diagnosing the activity of disease in patients with Graves' disease (exophthalmos), sarcoidosis, and rheumatoid arthritis. The pathophysiological premises to imaging, starting from an analysis of cells expressing sstr, binding affinity of octreotide for sstr, in vivo uptake of Octreoscan in lesions expressing or not sstr are discussed, as is the possible role of quantitative receptor scintigraphy in improving diagnostic accuracy based on tumor expression of sstr.

Nuclear medicine in emergency.

The role of a procedure depends not only on its own capabilities but also on a cost/effective comparison with alternative techniques giving similar information. Starting from the definition of emergency as a sudden unexpected occurrence demanding immediate action, the role of nuclear medicine (NM) is difficult to identify if it is not possible to respond 24 h a day, 365 days a year, to clinical demands. To justify a 24 h NM service it is necessary to reaffirm the role in diagnosis of pulmonary embolism in the spiral CT era, to spread knowledge of the capabilities of nuclear cardiology in reliably diagnosing myocardial infarction (better defining admission and discharge to/from the emergency department), to increase the number of indications. Radionuclide techniques could be used as first line, alternative, complementary procedures in a diagnostic tree taking into account not only the diagnosis but also the connections with prognosis and therapy in evaluating cerebral pathologies, acute inflammation/infection, transplants, bleeding, trauma, skeletal, hepatobiliary, renal and endocrine emergencies, acute scrotal pain.

Enhanced detection of vesicoureteric reflux with isotopic cystography.

We compared the accuracy of isotope cystography (IC) and fluoroscopic cystourethrography (FC) in detecting vesicoureteric reflux (VUR) in children. FC and IC were performed in 124 children, 56 boys and 68 girls, aged 1 month to 9.2 years (mean 2.1 years), admitted consecutively for suspected VUR over a 10-month period. VUR was diagnosed by one or both studies in 51 of 124 (41%) patients. The two methods were concordant for the detection of VUR in 84% of kidney-ureter units and in 93% for the detection or exclusion of severe VUR. IC detected VUR more accurately than FC, both when all grades of VUR were considered together (P=0.00001) and when only severe reflux was considered (P=0.004). VUR was missed by FC in 23 of 51 (45%) subjects. Of those 23, 12 had severe VUR detected on one side at least by IC. VUR was missed by IC in 3 subjects. IC is significantly more accurate than FC in the initial diagnosis of VUR, even of severe grade. IC is the method of choice for the first diagnosis of VUR. Boys with VUR diagnosed by IC also need FC to investigate for posterior urethral valves.